Identification of novel mutations by targeted exome sequencing and the genotype-phenotype assessment of patients with achromatopsia.
J Transl Med
; 13: 334, 2015 Oct 22.
Article
en En
| MEDLINE
| ID: mdl-26493561
ABSTRACT
BACKGROUND:
Achromatopsia (ACHM) is a severe congenital autosomal recessive retinal disorder caused by loss of cone photoreceptors. Here, we aimed to determine the underlying genetic lesions and phenotypic correlations in two Chinese families with ACHM.METHODS:
Medical history and clinical evaluation were obtained from both families. Targeted exome sequencing (TES) was performed on 201 disease-causing genes of inherited retinal dystrophies to screen for ACHM causative mutations in the two probands.RESULTS:
The compound heterozygous mutations in CNGA3 (c.1074G > A, p.W358X; c.1706G > A, p.R569H) were identified in the first proband, and a novel homozygous mutation (c.968C > A, p.A323D) was detected in the other pedigree. The proposed topological model of the CNGA3 polypeptide suggested that the missense mutations primarily affected the transmembrane helix 5 and the cGMP-binding domain, respectively. Crystal structure modeling of the cyclic nucleotide-gated cation channel α-3 (CNGA3) protein encoded by the CNGA3 gene revealed an abnormal combined structure generated by R569H.CONCLUSIONS:
We firstly used the TES approach to identify genetic alterations in patients with ACHM. We uncovered three mutations in CNGA3, including one novel mutation. Our results not only expand the genotypic spectrum for CNGA3 mutations, but also demonstrate that the TES approach is a valuable tool for molecular diagnosis.
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Análisis Mutacional de ADN
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Defectos de la Visión Cromática
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Exoma
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Mutación
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Adult
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Child
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Female
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Humans
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Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Transl Med
Año:
2015
Tipo del documento:
Article
País de afiliación:
China